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Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

ABSTRACT: Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confer tolerance of cadmium or arsenic. We identified 106 genes required for cadmium resistance and 110 genes required for arsenic resistance, with a highly significant overlap of 36 genes. A subset of these 36 genes account for almost all proteins required for incorporating sulfur into the cysteine-rich glutathione and phytochelatin peptides that chelate cadmium and arsenic. A requirement for Mms19 is explained by its role in directing iron-sulfur cluster assembly into sulfite reductase as opposed to promoting DNA repair, as DNA damage response genes were not enriched among those required for cadmium or arsenic tolerance. Ubiquinone, siroheme, and pyridoxal 5'-phosphate biosynthesis were also identified as critical for Cd/As tolerance. Arsenic-specific pathways included prefoldin-mediated assembly of unfolded proteins and protein targeting to the peroxisome, whereas cadmium-specific pathways included plasma membrane and vacuolar transporters, as well as Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator that controls expression of key genes required for cadmium tolerance. Notable differences are apparent with corresponding screens in the budding yeast Saccharomyces cerevisiae, underscoring the utility of analyzing toxic metal defense mechanisms in both organisms.

SUBMITTER: Guo L

PROVIDER: S-EPMC5068951 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

Guo Lan L Ganguly Abantika A Sun Lingling L Suo Fang F Du Li-Lin LL Russell Paul P

G3 (Bethesda, Md.) 20161013 10

Heavy metals and metalloids such as cadmium [Cd(II)] and arsenic [As(III)] are widespread environmental toxicants responsible for multiple adverse health effects in humans. However, the molecular mechanisms underlying metal-induced cytotoxicity and carcinogenesis, as well as the detoxification and tolerance pathways, are incompletely understood. Here, we use global fitness profiling by barcode sequencing to quantitatively survey the Schizosaccharomyces pombe haploid deletome for genes that confe ...[more]

PMID: 27558664

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Project description:The expected increase of sustainable energy demand has shifted the attention towards bioenergy crops. Due to their know tolerance against abiotic stress and relatively low nutritional requirements, they have been proposed as election crops to be cultivated in marginal lands without disturbing the part of lands employed for agricultural purposes. Arundo donax L. is a promising bioenergy crop whose behaviour under water and salt stress has been recently studied at transcriptomic levels. As the anthropogenic activities produced in the last years a worrying increase of cadmium contamination worldwide, the aim of our work was to decipher the global transcriptomic response of A. donax leaf and root in the perspective of its cultivation in contaminated soil. In our study, RNA-seq libraries yielded a total of 416 million clean reads and 10.4 Gb per sample. De novo assembly of clean reads resulted in 378,521 transcripts and 126,668 unigenes with N50 length of 1812 bp and 1555 bp, respectively. Differential gene expression analysis revealed 5,303 deregulated transcripts (3,206 up- and 2,097 down regulated) specifically observed in the Cd-treated roots compared to Cd-treated leaves. Among them, we identified genes related to "Protein biosynthesis", "Phytohormone action", "Nutrient uptake", "Cell wall organisation", "Polyamine metabolism", "Reactive oxygen species metabolism" and "Ion membrane transport". Globally, our results indicate that ethylene biosynthesis and the downstream signal cascade are strongly induced by cadmium stress. In accordance to ethylene role in the interaction with the ROS generation and scavenging machinery, the transcription of several genes (NADPH oxidase 1, superoxide dismutase, ascorbate peroxidase, different glutathione S-transferases and catalase) devoted to cope the oxidative stress is strongly activated. Several small signal peptides belonging to ROTUNDIFOLIA, CLAVATA3, and C-TERMINALLY ENCODED PEPTIDE 1 (CEP) are also among the up-regulated genes in Cd-treated roots functioning as messenger molecules from root to shoot in order to communicate the stressful status to the upper part of the plants. Finally, the main finding of our work is that genes involved in cell wall remodelling and lignification are decisively up-regulated in giant reed roots. This probably represents a mechanism to avoid cadmium uptake which strongly supports the possibility to cultivate giant cane in contaminated soils in the perspective to reserve agricultural soil for food and feed crops.

Dataset Information

Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

Publications

Global Fitness Profiling Identifies Arsenic and Cadmium Tolerance Mechanisms in Fission Yeast.

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